The major objective of these studies is to delineate the importance of immune responses within the central nervous system (CNS) of mouse strains which vary in their resistance to neurotropic rabies virus. It has been determined that rabies virus neutralizing antibody was not present in the cerebrospinal fluid (CSF) of resistant or susceptible strains of mice 3, 5, 7 or 10 days following intraperitoneal inoculation of street rabies virus (SRV). Antibody was present, however, in resistant strains on the 15th day and thereafter, but seldom was detected in the CSF of susceptible A.SW, A/WySn or athymic (nude) mice. It is not known whether the paucity of neutralizing antibody in the CSF of these mice correlated with their susceptibiliy, or whether the delayed appearance of antibody in the CSF of resistant mice (greater than 10 days) was irrelevant as a mechanism of resistance to infection. Furthermore in resistant mice, there was no correlation between CSF antibody titer and the clinical course of disease; mice which developed clinical signs of illness but survived (DBA/2, BALB/c) had titers similar to mice which did not develop clinical illness(SJL, CBA/J). In addition, antibody never was detected in the CSF of mice which had serum neutralizing antibody titers of greater than 1:320. The future course of this project will focus on understanding the protective, if any, role of neutralizing antibody in the CSF and whether it is synthesized locally in the CNS. In addition, the importance of interferon and T-lymphocytes in the CSF will be assessed in mice strains which vary in their susceptibility to SRV.